Methadone: A Major Driver of Prescription Painkiller Overdose Deaths

Methadone accounts for nearly 1 in 3 prescription painkiller overdose deaths in the U.S., even though only 2% of prescriptions for opioid painkillers are for this drug, according to a new report by the Centers for Disease Control and Prevention (CDC). The report also found that six times as many people died of methadone-related overdoses in 2009, compared with a decade earlier.

The research showed further that about 4 million methadone prescriptions for pain are written annually and the drug causes about 5,000 overdose deaths each year. While most overdoses involve mixtures of drugs, methadone accounted for 40% of deaths involving a single drug in 2009, twice as many as for any other prescription opioid.

“Deaths from opioid overdose have increased fourfold in the past decade, and methadone now accounts for nearly a third of opioid-associated deaths,” said CDC director Dr. Thomas R. Frieden in a statement.

For the report, the CDC analyzed national data on prescription sales and overdose death rates from 1999 to 2010, as well as 2009 data on deaths from methadone and other opioids, such as Oxycontin, Vicodin and heroin, from 13 states covered by the Drug Abuse Warning Network.

Methadone is best known for its use in addiction treatment, but the deaths included in the CDC report are not associated with these programs. “We’re not talking about methadone maintenance treatment in this data,” said Frieden in a press teleconference on Tuesday. “All of the evidence suggests that the increase in methadone related deaths is related to increased use of methadone to treat pain.”

The drug has been used safely to treat addiction since the 1960s, but in recent years prescriptions for pain relief have increased. In Nov. 2006, federal health officials warned against using methadone as a first-choice pain reliever, because it’s so tricky to prescribe safely, but prescriptions haven’t declined much. So, in tandem, rates of nonmedical use of methadone and fatal overdoses have risen; the drugs involved in these cases are typically diverted from pain treatment, not from addiction treatment programs.

So why is methadone so much more deadly when used to treat chronic pain? Because it’s long-lasting and it builds up in the body. Methadone kills pain for about six hours on average, but with accumulating doses, it can slow a person’s breathing and disrupt heart rhythm — effects that can last for days. (These problems can become deadly on their own, but are even riskier when users take drugs like alcohol or Valium with methadone.) This means that taking methadone three times a day — exactly as prescribed — can lead to a potentially fatal overdose if the person is not fully tolerant to the drug. Worse, the effects vary widely from person to person.

The methadone prescription problem goes back to the late 1990s and early 2000s, when drug addicts discovered that a new painkiller called Oxycontin could be snorted or injected to produce an intense high — and get around the pill’s time-release mechanism. Oxycontin’s manufacturer, Purdue, was eventually fined $634 million for selling the medication as less addictive than other opioids. With law enforcement scrutiny intensifying on Oxycontin prescribing, doctors began looking for a drug that had similarly long-lasting effects on pain.

Methadone fit the bill perfectly. Not only is it one of the longest acting opioid drugs, it’s also generic and about 12 times cheaper than brand-name Oxycontin. Its long history of safe use in addiction treatment may also have made it look less risky than it is, leading many insurers and some state health programs to put it on their formularies as a preferred drug, meaning that it would be covered when other similar medications like Oxycontin would not be.

But there’s a big difference between addiction patients and pain patients: people using methadone for maintenance treatment have a long history of opioid use — that’s why they’re in treatment — and therefore, a high tolerance to the entire class of drugs. That means that as a population, they are already self-selected to be able to manage large doses of opioids successfully. But that’s not true for many pain patients, which is why the CDC report states bluntly that, “[M]ethadone should not be prescribed to opioid-naive patients.” Yet as the report shows, about one-third of all pain patients who were prescribed methadone had no prescriptions for another opioid in the month before they received the drug.

Also, the doses of methadone used in maintenance treatment for addiction are very carefully controlled. Initial doses are small — the difference between appropriate and dangerous doses of methadone is slight — and patients aren’t allowed to take the drug home until they have proved through months of daily program attendance and drug-free urine tests that they are tolerant to it and can use it safely. In contrast, most methadone prescribing for pain is done by general practitioners and other nonspecialists who don’t have training in pain management.

Even the Food and Drug Administration‘s own labeling information regarding appropriate doses of methadone for pain was inaccurate, until 2006 when an expose by the Charleston Gazette revealed that following the package insert could cause overdose, especially in patients who did not have prior exposure to opioids. Unlike in methadone maintenance treatment, pain patients are not monitored when they take the drug initially.

“There are plenty of safer alternatives to methadone,” said Frieden, noting that for most pain patients, there are other opioids, other types of drugs and nonpharmacological approaches like physical therapy that can help. He added, however, that the CDC wants to make sure the drug is available for cancer patients, people in addiction treatment programs and others for whom it is found to be the best option.

As for using the generic drug to cut costs, Frieden says methadone is a bad bargain. “Using methadone [to reduce spending in pain care] is pennywise and poundfoolish,” he said. “It results in many more emergency rooms visits and higher societal costs in deaths.”

Maia Szalavitz is a health writer at TIME.com. Find her on Twitter at @maiasz. You can also continue the discussion on TIME Healthland’s Facebook page and on Twitter at @TIMEHealthland.